The presence of a 1.4 x 10 to the six power dalton-stranded RNA in intracellular virus-like particles (the killer plasmid or killer virus) in Saccharomyces cerevisiae enables cells to secrete a protein toxin and be immune to this toxin. We have defined 28 chromosomal genes (called makl, . . .) needed to replicate or maintain the killer plasmid. One of these genes is spe2, the structural gene for adenosylmethionine decarboxylase. Thus, spermidine or spermine is needed for killer plasmid replication. Methods for complementation and genetic mapping of these genes have been devised. We have discovered a nineteenth chromosome of yeast. Mutations in any of four chromosomal genes (called ski) make cells superkillers. These mutations make certain mak genes dispensable for killer plasmid replication. We have also found a plasmid-coded mak gene and a plasmid-coded ski gene.